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A Brach del Prever

Publications and source records attributed to A Brach del Prever.

At least 19 recordsLinked to original sources

ErbB2 and bone sialoprotein as markers for metastatic osteosarcoma cells.

Osteosarcoma is the most common malignant bone neoplasia occurring in young patients in the first two decades of life, and represents 20% of all primitive malignant bone tumours. At present, treatment of metastatic osteosarcoma is unsatisfactory. High-dose chemotherapy followed by CD34+ leukapheresis rescue may improve these poor results. Neoplastic cells contaminating the apheresis may, however, contribute to relapse. To identify markers suitable for detecting osteosarcoma cells in aphereses we analysed the expression of bone-specific genes (Bone Sialoprotein (BSP) and Osteocalcin) and oncogenes (Met and ErbB2) in 22 patients with metastatic osteosarcoma and six healthy stem cell donors. The expression of these genes in aphereses of patients affected by metastatic osteosarcoma was assessed by RT-PCR and Southern blot analysis. Met and Osteocalcin proved to be not useful markers since they are positive in aphereses of both patients with metastatic osteosarcoma and healthy stem cell donors. On the contrary, BSP was expressed at significant levels in 85% of patients. Moreover, 18% of patients showed a strong and significantly positive (seven to 16 times higher than healthy stem cell donors) ErbB2 expression. In all positive cases, neoplastic tissue also expressed ErbB2. Our data show that ErbB2 can be a useful marker for tumour contamination in aphereses of patients affected by ErbB2-expressing osteosarcomas and that analysis of Bone Sialoprotein expression can be an alternative useful marker.

Adolescent↗

High-dose chemotherapy in the treatment of relapsed osteosarcoma: an Italian sarcoma group study.

PURPOSE: To study the feasibility and activity of two courses of high-dose chemotherapy (HDCT) in patients with osteosarcoma in metastatic relapse. PATIENTS AND METHODS: Patients with high-grade osteosarcoma in metastatic relapse (multiple metastases or solitary metastasis at intervals of less than 30 months) were eligible for study. High-dose chemotherapy consisted of carboplatin and etoposide followed by stem-cell rescue. A second course was planned 4 to 6 weeks after the first. Surgery was performed before or after HDCT. RESULTS: Thirty-two patients were enrolled onto the study. At the end of the treatment, 25 patients were in complete remission (CR), six were alive with disease progression, and one died of toxicity. At present, 14 patients are alive with a median survival time of 23 months from study entry: four are in first CR, three are in second CR, and one is in fourth CR. Six patients are alive with disease. Eighteen patients (56%) died: 17 of disease and one of toxicity. Transplantation-related mortality was 3.1%. The relapse or progression disease rate was 84.4%. The 3-year overall survival rate is 20% and the 3-year disease-free survival rate is 12%. CONCLUSION: HDCT combined with surgery is feasible and can induce CR in a large portion of patients. Two points, however, need to be considered: only patients who are chemosensitive to induction treatment can obtain CR after HDCT, and the length of remission is short, because most patients relapse. Thus novel strategies are needed to maintain the remission status or to treat patients who do not respond to induction treatment.

Adolescent↗

Neoadjuvant chemotherapy for Ewing's sarcoma of bone: no benefit observed after adding ifosfamide and etoposide to vincristine, actinomycin, cyclophosphamide, and doxorubicin in the maintenance phase--results of two sequential studies.

BACKGROUND: Ifosfamide (IF) alone or combined with etoposide (ET) was reported to be effective in the treatment of patients with Ewing's sarcoma who relapsed after treatment with the VACA regimen, which consisted of vincristine (VC), actinomycin (AC), cyclophosphamide (CP), and doxorubicin (AD). The purpose of this article is to report the results achieved in a new neoadjuvant protocol in which IF and ET were added to the conventional VACA regimen and administered to patients with localized disease. METHODS: In this study, eighty-two patients were treated between May 1988 and October 1991. Chemotherapy consisted of two induction cycles of VC/CP/AD followed by alternating cycles of VC/AD/CP, VC/IF/AC, IF/ET, and VC/CP/AC after local treatment. Twenty-two patients (27%) were treated with surgery only, 22 (27%) underwent surgery followed by radiation therapy, and 38 (46%) received radiotherapy only. RESULTS: At a median follow-up of 6.7 years (range, 4-9 years), 43 patients (52%) remained continuously disease free, and 39 relapsed (34 with metastases, 4 with local recurrence and metastases, and 1 with a local recurrence). These results were similar to those obtained at the same institute in a previous neoadjuvant study (March 1983 and April 1988) that included 108 patients treated with the conventional 4-drug regimen. The 5-year disease free and overall survival in the current study were 54% and 59%, respectively, and in the first study were 50% and 56%, respectively. CONCLUSIONS: The comparison of these two sequential studies, although not randomized, referred to homogeneous groups of patients observed at the same institution who were treated by the same medical team. No advantage was observed when IF and ET were added to the VACA regimen.

Adolescent↗

Neoadjuvant chemotherapy for extremity osteosarcoma--preliminary results of the Rizzoli's 4th study.

A neoadjuvant chemotherapy protocol (1/93-1/95) for extremity osteosarcoma preoperatively using high-dose methotrexate (HDMTX) as single agent per cycle and three different combinations of other drugs (CDP/IFO,CDP/ADM,IFO/ADM) is reported. The four drugs were used postoperatively as single agents. Treatment was uniform, but suspended earlier if total necrosis was attained. An improvement was found in the results of the previous study using only IFO postoperatively, with 16/119 patients (97%) avoiding amputation, and 38 (32%) attaining complete necrosis. At a 3-year (2-4 years) mean follow-up, 92 patients (76%) remained continuously disease-free, 2 died of chemotherapy-related toxicity and 25 suffered relapse. Projected 3-year DFS also improved (75% vs. 60%; p = 0.04). Despite limb salvage, local recurrences (6.3%) and infections were few, although postoperative chemotherapy was restarted within a week. Therefore, until new effective drugs are found, expertise in using the four known drugs may improve cure rate and help to avoid amputation in almost all patients.

Adolescent↗

Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatin.

PURPOSE: In osteosarcoma of the extremity, a strong correlation between chemotherapy-induced necrosis and prognosis has been reported. The aim of this study was to investigate the possible factors that influence histologic response to primary chemotherapy. PATIENTS AND METHODS: In 272 patients with high-grade osteosarcoma of the extremity preoperatively treated with high-dose methotrexate (HDMTX), cisplatin (CDP), and doxorubicin (ADM), the histologic response to chemotherapy was evaluated and graded as complete (no viable tumor cells) or incomplete (persistence of viable tumor cells). Several factors, such as metastatic disease to the lung at diagnosis, sex, age, site and tumor volume, histologic subtype, serum alkaline phosphatase, lactate dehydrogenase (LDH), and methotrexate (MTX) pharmacokinetics were investigated to test their predictive significance on histologic response. RESULTS: Fifty-one patients with localized disease (20.6%) and none of the 25 patients with metastatic disease at presentation had a complete histologic response (P = .006). After multivariate analysis, performed on patients with localized disease only, MTX serum peak (> or = 700 micromol/L) and histologic subtype were proven to be significant predictive factors of histologic response. A complete response was seen in 28.8% of patients with 700 micromol/L or greater MTX serum levels and in 9.9% of those patients with lower levels (P = .001). The chondroblastic subtype was less responsive (6.1% of complete response), compared with the osteoblastic (16.3%), fibroblastic (33.3%), and telangiectatic (42.3%). CONCLUSION: Patients with metastatic osteosarcoma and localized chondroblastic osteosarcoma have a reduced chemosensitivity to primary chemotherapy with MTX, CDP, and ADM. MTX serum peak significantly influences tumor necrosis. A dose adaptation of MTX is recommended to obtain a serum peak of 700 micromol/L or greater when MTX is infused in 6 hours.

Adolescent↗

Feasibility of high-dose chemotherapy and autologous peripheral blood stem cell transplantation in children with high grade osteosarcoma.

An Italian-Scandinavian treatment and research protocol with high-dose chemotherapy and double peripheral blood stem cell (PBSC) transplantation has been designed in an attempt to improve overall results of children with metastatic osteosarcoma (OST). Six patients, aged 12-17 years, underwent PBSC mobilization with CY 4 g/m2 and VP-16 600 mg/m2 followed by G-CSF (n = 4 with recurrent disease) or ifosfamide 15 g/m2 plus G-CSF (n = 2 with synchronous metastases). The target dose of CD34+ cells for two transplant procedures was 8 x 10(6)/kg or more; conditioning regimen for both the grafts consisted of carboplatin 375 mg/m2/day for 4 days and VP16 450 mg/m2/day for 4 days. The first transplant was planned 2-4 weeks after the mobilization, the second transplant 4-6 weeks after the first graft. In three patients a single course of CY-VP16 mobilised a total number of CD34+ sufficient for two transplants; in the patient who did not obtain the target dose of CD34+ cells a bone marrow harvest was added. In the two other children high-dose ifosfamide failed to achieve the required CD34+ number: one patient underwent a single transplant procedure, one patient was successfully mobilized with doxorubicin 90 mg/m2 plus G-CSF. Patients underwent a median of two collections (range 2-4). Leukapheresis resulted in the collection of a median of 8.9 CD34+ cells/kg (range 1.3-14.8). The median time to granulocyte count recovery to more than 0.5 x 10(9)/l was 10 days (range 9-14 days) after the first graft and 11 days (range 10-12 days) after the second graft, respectively. Platelets recovered to 50 x 10(9)/l at a median of 11 (range 10-30 days) and 13 days (range 10-28) respectively after the first and the second graft. Conditioning regimen was well tolerated in all patients with mild extra haematological toxicity, also following the second transplant. Two patients grafted with metastases at diagnosis are alive and disease free 3 and 7 months from the transplant. One of the four patients transplanted for recurrent disease developed pulmonary metastases 2 months after the procedure; one patient is alive with significant reduction of tumor mass 1 month after the first transplant, one patient is alive without evidence of disease 9 months from the second transplant and one after a complete metastasectomy (tumor necrosis >90%) which followed the second transplant. With the limits of the small number of cases and the short follow-up, these preliminary results show that this approach may be promising for the treatment of patients with metastatic OST who currently are not cured by conventional-dose regimens.

Adolescent↗

Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy.

BACKGROUND: Most of the studies of the treatment of non-metastatic osteosarcoma of the extremity have reported results in terms of probability of survival up to five years with a minimum follow-up of less than two to three years. Definition of reliable indicators of prognosis and predictive factors for survival require mature data derived from a long-term survival analysis. PATIENTS AND METHODS: A review of 127 patients with non-metastatic osteosarcoma of the extremity, treated between March 1983 and June 1986, was performed. The treatment protocol consisted of primary chemotherapy with MTX (randomization to high vs. moderate dosages) and CDP followed by surgery. Postoperatively, patients with < 60% tumor necrosis received ADM and BCD; those with tumor necrosis > or = 60% < 90% (Fair Responders FR) were given MTX, CDP and ADM. Up to January 1984, patients with tumor necrosis > 90% received MTX and CDP only, and after then they were given the same treatment as for FR. A multivariate analysis to test predictive factors for survival was performed. RESULTS: With a median follow-up of 134 months (range 114-153), the 12-year DFS was 46%. A good histologic response, an LDH baseline value within the normal range, and the use of high-dose MTX were positive predictive factors for DFS. With a median time of observation for survivors of 130 months, the 12-year overall survival was 53%. None of the patients who relapsed with local or distant recurrences other than lung metastasis are now alive. Patients with a relapse-free interval longer than 24 months had a significantly better post-relapse survival than those with a shorter relapse-free interval (40% vs. 7%; P = 0.0159). All of the patients who were not surgically treated had disease progression and died within 40 months after the first recurrence. The surgically-treated patients had a 30% post-relapse survival probability. CONCLUSIONS: In non-metastatic osteosarcoma of the extremity, chemotherapy-induced tumor necrosis, the baseline LDH serum value and the use of HDMTX are significant predictive factors for DFS. The relapse-free interval and the possibility of metastasectomy are significant factors conditioning the post-relapse survival.

Adolescent↗

Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing's sarcoma of the extremities.

PURPOSE: This study was performed to assess the prognostic value of the proposed histopathologic method to evaluate the response of the primary tumor to preoperative chemotherapy in Ewing's sarcoma. PATIENTS AND METHODS: The response to chemotherapy was evaluated from the specimens of 118 Ewing's sarcoma patients, who were preoperatively treated by chemotherapy alone. Responses were graded I to III (macroscopic viable tumor, microscopic viable tumor, and no viable tumor cells, respectively). Follow-up data were available for all patients, with a mean follow-up duration of 86 months (range, 30 to 158). RESULTS: A statistically highly significant difference was observed in outcome among the three groups of patients. For patients with total necrosis (grade III response), the estimated 5-year disease-free survival rate was 95%, in contrast to 68% for grade II responders and 34% for grade III responders (P < .0001). This difference was also confirmed when any single group was compared with the other groups. Among the parameters tested, patient age and the size of tumor had some prognostic value. CONCLUSION: The proposed histopathologic grading, to evaluate the effect of chemotherapy on the primary tumor, had the strongest correlation to clinical outcome. This method could therefore be used to identify patients with a high risk of recurrent disease. These patients could be randomized to receive alternative postoperative treatments to investigate whether more aggressive therapies will improve outcome.

Adolescent↗

CNS-85 trial: a cooperative pediatric CNS tumor study--results of treatment of medulloblastoma patients.

Between 1985 and 1989, 38 children with newly diagnosed medulloblastoma entered our therapeutic protocol. After surgery and postoperative staging assessments, patients were assigned to risk groups. Eleven with "standard-risk" (SR) tumors were treated with radiation therapy alone, while 27 with "high-risk" (HR) tumors received radiation therapy plus adjuvant chemotherapy with vincristine, methotrexate, VM-26, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). After a minimum follow-up of 5 years (range 5-9 years) 21/38 children had developed a recurrence or progression of their disease and 19/38 patients had died. Five-year event-free survival rates and 5-year total survival rates for all 38 patients were 47.4% and 50% respectively. The event-free survival rates at 5 years for SR and HR patients separately were 27.3% and 55.6%, respectively. The corresponding 5-year total survival rates were 27.3% and 59.3%. The differences were not statistically significant. Univariate analysis showed age at diagnosis to be the most important prognostic factor. Infants aged 5 years or less had a significantly shorter event-free survival time than older patients (P = 0.00897). Similar effects were found when total survival time was considered. There were significant differences in outcome in patients receiving different doses of radiation, suggesting a dose-response relationship. A Cox stepwise multivariate analysis showed age at diagnosis as the only independent prognostic factor. Variables relating to treatment entered the model, suggesting that chemotherapy could play an important role in determining outcome.

Adolescent↗

[Neoadjuvant treatment of Ewing's sarcoma: results obtained in 122 patients treated with a 6-drug chemotherapeutic protocol (vincristine, adriamycin, cyclophosphamide, dactinomycin, ifosfamide and etoposide)].

From January 1988 to October 1991, one hundred and twelve patients with non metastatic Ewing's sarcoma of bone were treated with a 6 drugs neoadjuvant chemotherapy protocol (IOR/Ew2) in which, to the four drugs usually used in the treatment of this tumor (vincristine, adriamycin, cyclophosphamide and dactinomycin), Ifosfamide and VP-16 were added. The local treatment consisted of radiation therapy in 52 cases, a surgical treatment was performed in 27 cases and in the remaining 33 cases both the previous treatments were used. At a mean follow-up of 4.5 years (3-6.5), 62 patients (55.3%) remained continuously free of disease and 50 relapsed: 41 with metastases, 8 with mestastases and local recurrence and 1 with local recurrence alone. These results do not differ from the ones obtained in our Institution in 98 patients treated between 1983 and 1988 with a neoadjuvant protocol (IOR/Ew1) in which only VCR, ADM, CTX and actD were used (3 year CDFS: IOR/Ew2 = 60.7%-IOR/Ew1 = 55.1%). In IOR/Ew2 a higher DFS rate was observed in the patients with tumor located in the axile bones in comparison with that obtained in the previous study (IOR/Ew2 = 48.6%, IOR Ew1 = 25.6%). Despite the fact that these results came from a not-randomized study, the authors conclude that the addition of Ifosfamide and VP-16 to the four drugs standard regimen do not improve the outcome of patients with Ewing's sarcoma of bone, with the possible exception of the patients with tumor located in the axile bones. This data should be confirmed in further and larger studies.

Adolescent↗

Primary chemotherapy and delayed surgery for non-metastatic telangiectatic osteosarcoma of the extremities. Results in 28 patients.

28 patients with telangiectatic osteogenic sarcoma of the extremities were treated between March 1983 and March 1990 with neoadjuvant chemotherapy according to two different protocols activated successively. With the first protocol, patients preoperatively received high dose methotrexate (HDMTX)-cisplatinum (CDP) and postoperatively, depending on the histological response, either HDMTX-CDP-doxorubicin (ADM) or ADM-"BCD". With the second protocol patients were preoperatively treated with HDMTX-CDP-ADM and postoperatively either with the same drugs or with the same drugs plus ifosfamide and VP-16. Preoperatively, CDP was delivered intraarterially. A good histological response (tumour necrosis > 90%) was observed in 25 patients (89%) and at a mean follow-up of 5 years (2-9 years) 23 patients (82%) remained continuously disease-free and 5 developed lung metastases. These results are better than those obtained in 272 contemporary cases of conventional osteosarcoma of the extremities treated with the same protocols (62% good histological responses and 61% continuously disease-free survival).

Adolescent↗

[Use of cyclosporin and verapamil in association with chemotherapy in the treatment of pediatric patients with advanced-stage neoplasms. A pilot study].

Multidrug resistance represents one of the most important factors that may lead to a therapeutic failure in some patients affected by malignancies. One of the best known mechanisms is linked to the genic amplification or the overproduction of a membrane glycoprotein, GP170, that is the product of the gene MDR1. The existence of drugs (calcium blockers, cyclosporine, tamoxifen, reserpine, quinidine) able to bind themselves to gp170 and to paralyze its activity in vitro is well known. We studied 20 pediatric patients (median age 9 years) affected by acute lymphoblastic leukemia (ALL), osteosarcoma, neuroblastoma and medulloblastoma, in advanced stage of disease. We employed in all cases the association of cytostatics with verapamil (50-70 mg/m2 i.v.) and cyclosporine (5-8 mg/kg i.v.) with different infusion schedules. In leukemias we administered vincristine (1.5 mg/m2), and daunomycin (40 mg/m2), in solid tumors VP16 (150 mg/m2) and adriamycin (60 mg/m2). Seventy-two therapeutic courses were performed: 39 in ALL, 16 in osteosarcoma, 16 in neuroblastoma and 1 in medulloblastoma. On the whole 5 complete remissions were achieved in ALL patients and 1 in an osteosarcoma patient. We did not observe a significant myelosuppression during treatment, therefore few infectious complications occurred; furthermore electrocardiographic changes have been mild and promptly resolved after temporary discontinuation of verapamil infusion. Our data suggest a synergy of verapamil and cyclosporine in the inhibition of multidrug resistance induced by gp170, without the occurrence of heavy toxicity. The results obtained in ALL patients are encouraging., especially in view of a possible subsequent bone marrow transplantation, while in solid tumors they are not as satisfying.

Adolescent↗

Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin.

BACKGROUND: Neoadjuvant chemotherapy is the most accepted treatment for localized osteosarcoma. This has led to a great improvement in limb-sparing surgery and in disease-free survival. Patients with a good response to preoperative chemotherapy showed a higher disease-free survival rate. Current studies examine the possibility of patients whose limbs could be rescued with a poor necrosis and a reduction of the side effects related to aggressive treatments. METHODS: Between September 1986 and December 1989, 164 patients entered the second neoadjuvant study conducted at the Rizzoli Institute, Bologna, Italy, for non-metastatic osteosarcoma of the extremities. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate intravenously (i.v.) followed by cisplatin intraarterially and doxorubicin i.v. After surgery, patients classified as good responders (> 90% tumor necrosis) received three more cycles of these drugs, whereas poor responders (< 90% tumor necrosis) had more chemotherapy, which included ifosfamide and etoposide in addition to the other three drugs. RESULTS: Limb salvage was performed in 83% of cases. At an average follow-up of 54 months (36-76), 109 patients (66%) were continuously disease-free, 2 died from doxorubicin cardiotoxicity, and 52 experienced metastases and 3 had local recurrence. In two of these three patients, metastases followed local recurrence. The 5-year actuarial continuously disease-free survival rate was 63%, with no differences between good and poor responders. Excluding 20 patients who had major protocol violations, the projected continuous disease-free survival rate was 71%. CONCLUSIONS: With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of nonmetastatic osteosarcoma of the extremities, avoiding amputation in most cases. Ifosfamide and etoposide seem to be effective in patients who did not respond to preoperative chemotherapy.

Adolescent↗

Ectopic neuroblastoma of the thoracic wall: a case report.

A case of thoracic neuroblastoma arising at the anterior mammillary line from the inner surface of the second and third right rib in a 17-month-old male child is reported. Primary surgery allowed excision of the mass. According to the histologic, histochemical, and molecular features of the tumor, all consistent with the diagnosis of neuroblastoma stage 2, the patient underwent adjuvant chemotherapy and, after 2 years, he is alive and disease free at follow-up. In view of different clinical and therapeutical approaches, only a strict adherence to histopathologic criteria allows differentiation of neuroblastoma, even in a very unusual anatomical site, from other small-cell, peripheral neoplasms presumably arising from the embryonic neural crest, such as Askin's tumor, neuroepithelioma, and ectomesenchymoma. The site of origin of these tumors is an important diagnostic clue but can be misleading: only careful microscopic evaluation and molecular analysis lead to incontrovertible diagnosis and yield correct clinical management.

Diagnosis, Differential↗

Results of a multicenter retrospective study on pediatric brain tumors in Italy.

This retrospective study was undertaken to evaluate the clinical characteristics, course and treatment of children (0-14 years of age) diagnosed with a primary CNS tumor during the period 1976-1982 in Italy. Four hundred and sixty-two patients (263 males and 199 females) were followed by 18 various neurosurgical and pediatric oncology centers. The histologic types most frequently reported were: medulloblastoma (23%), astrocytoma (16%), ependymoma (11%) and spongioblastoma (11%). Of the 388 patients who underwent surgery, radical excision was reported in 42%, partial excision in 32%, biopsy only in 6%, and unqualified surgery in 4%; 19% had no surgery. Radiotherapy and chemotherapy combined were administered in 61% of the 143 patients followed at pediatric oncology centers; 19% received radiotherapy alone, 3% chemotherapy alone, and 17% neither treatment. Forty-six percent of the patients were reported alive, 40% dead, and 14% lost to follow-up. Performance status was identified for 62 patients. The investigation revealed marked differences in the therapeutic treatment administered, thus precluding valid data analysis. This emphasizes the need to coordinate efforts among the institutions and the disciplines involved in the treatment of this form of childhood cancer.

Adolescent↗

[Brain tumors].

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Brain Neoplasms↗

Glucose metabolism in children with acute lymphoblastic leukemia treated according to two different L-asparaginase schedules.

Oral glucose tolerance tests were performed in 47 children with acute lymphoblastic leukemia (ALL), treated according to 2 consecutive protocols. Glucose and insulin values were assessed before and after L-asparaginase (L-asp). 30 children (group A) received L-asp as a single-agent consolidation course, after achieving remission with vincristine (VCR) and prednisone (PDN). Normal insulin and glucose levels were found in all patients before L-asp; 4 children (13%) had a transient impaired glucose tolerance (IGT) after completing L-asp therapy. 17 children (group B) were given L-asp during induction therapy with VCR and PDN, and all achieved complete remission. 5 patients (23%) had IGT, without hypoinsulinemia, before L-asp administration. IGT normalized in 4 patients after L-asp, the other children developed a diabetes mellitus. Only 1 patient, with a normal IGT test before L-asp therapy, showed a transient IGT after L-asp. In patients with ALL, the presence of IGT before treatment may be related to leukemia. The concomitant use of steroids does not influence the incidence of IGT in our series. Our data reveal normal insulinemia in patients with IGT. Thus, the leukemic process itself may play a much more significant role in inducing abnormalities in carbohydrate metabolism.

Adolescent↗